Delineating the relationship between immune system aging and myogenesis in muscle repair

Abstract

How aging affects the communication between immune cells and myoblasts during myogenesis is unclear. We therefore investigated how aging impacts the cellular synchronization of these two processes after muscle injury. Muscles of old mice (20 months) had chronic inflammation and fewer satellite cells compared to young mice (3 months). After injury, young mice developed a robust, but transient inflammatory response and a stepwise myogenic gene expression program. These responses were impaired with age. Replacement of old bone marrow (BM) via heterochronic bone marrow transplantation (BMT) increased muscle mass and performance on locomotive and behavioural tests. After injury, Y-O BMT restored the immune cell and cytokine profiles to a young phenotype and enhanced satellite cell activity while O-O BMT amplified a late-onset proinflammatory response. In vitro, conditioned media from young or old macrophages had no effect or impaired myoblast proliferation, respectively. Thus, BM age negatively affects myogenesis by inhibiting myoblast proliferation.